The present invention relates to novel pyrimidine derivatives and pharmaceutically acceptable non-toxic salts thereof which possess an excellent inhibitory activity against gastric acid secretion, a pharmaceutical composition containing the same as an active ingredient, and a process for the preparation thereof.
For the treatment of peptic ulcer disease, various drugs such as antacid, anticholinergic agents, H2-receptor antagonist and proton pump inhibitor have been used. The advent of proton pump inhibitors has rekindled research activities in this field.
However, it has been pointed out that the irreversible mode of action by proton pump inhibitors may induce undesirable effects. Accordingly, various attempts to develop a reversible proton pump inhibitor (i.e., reversible acid pump antagonist) are being actively made. For example, European Patent Nos. 322,133 and 404,322 disclose quinazoline derivatives, European Patent No. 259,174 describes quinoline derivatives, and WO 91/18887 offers pyrimidine derivatives, as reversible proton pump inhibitors.
Further, the present inventors have also reported quinazoline derivatives in WO 94/14795 and pyrimidine derivatives in WO 96/05177 and WO 98/43968.
The present inventors have carried out further research to develop reversible acid pump antagonists with improved efficacy; and, as a result, have discovered that pyrimidine derivatives having one or more halogen groups at the 5- or 6-position of a pyrimidine nucleus or at the tetrahydroisoquinoline group of the 4-position of the pyrimidine nucleus exhibit excellent acid pump inhibition effects and inhibitory activity against gastric acid secretion.
Accordingly, it is a primary object of the present invention to provide novel pyrimidine derivatives having one or more halogen groups at the 5- or 6-position of a pyrimidine nucleus or at the tetrahydroisoquinoline group of the 4position of the pyrimidine nucleus, and pharmaceutically acceptable non-toxic salts thereof.
It is another object of the present invention to provide processes for preparing said compounds.
It is a further object of the present invention to provide pharmaceutical compositions for treating gastrointestinal diseases containing the same as an active ingredient.